title: Inhibition of nitric oxide synthesis enhances teratogenic effects induced by valproic Acid.
abstract: OBJECTIVE
  The mechanism of valproic acid (VPA)-induced teratogenicity is poorly known. This study was carried out to probe into the potential consequences of nitric oxide (NO) deprivation on VPA teratogenicity.
  
  
  METHODS
  On gestation day 8, mice were injected with a non-teratogenic dose (20 mg/kg) of the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl esther (L-NAME). Thirty minutes later, animals received a teratogenic dose of VPA (400 or 500 mg/kg). Developmental end-points were evaluated near the end of gestation.
  
  
  RESULTS
  After treatment with VPA at 400 mg/kg, 35.2% of fetuses exhibited skeletal teratogenesis. The rate of skeletally affected fetuses significantly increased to 53.7% after L-NAME co-administration. In the group treated with VPA at 500 mg/kg group, L-NAME pre-treatment increased the incidence of exencephaly from 5.4% to 22.2%.
  
  
  CONCLUSIONS
  Inhibition of NO synthesis can result in an enhancement of VPA-induced teratogenesis.
authors.affiliation: Department of Medicine and Aging Sciences, Faculty of Medicine, University G. d'Annunzio of Chieti-Pescara, Ortona, Italy. tiboni@unich.it
authors.forename: Gian Mario
authors.initials: GM
authors.lastname: Tiboni
authors.forename: Francesco
authors.initials: F
authors.lastname: Chiarelli
authors.forename: Alberto
authors.initials: A
authors.lastname: Verrotti
mesh_terms: D000818:Animals; D053898:Biosynthetic Pathways / Q000187:drug effects*; D000013:Congenital Abnormalities / Q000209:etiology; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D064793:Teratogenesis / Q000187:drug effects*; D013723:Teratogens / Q000494:pharmacology* / Q000633:toxicity; D014635:Valproic Acid / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D013723:Teratogens; D009569:Nitric Oxide; D014635:Valproic Acid
keywords: Valproic acid; axial skeletal defects; neural tube defects; nitric oxide synthesis inhibition; teratogenicity; teratological interaction